Gabapentin was originally identified and developed as a treatment for seizure disorders. During its clinical and post-clinical evaluation it was discovered that this agent showed significant clinical efficacy in alleviating neuopathic pain. Gabapentin has also been combined with morphine in acute and chronic pain models.
Additionally, Gabapentin reduces tactile allodynia and hyperalgesia, both mechanical and thermal, in animal models and has shown efficacy in the treatment of reflex sympathetic dystrophy (RSD), spasticity, and bipolar disorder.
[3H]Gabapentin labels human recombinant α2δ voltage-gated calcium channel with similar high affinity as compared to rat brain. [3H](L)-leucine has also been shown to specifically label the α2δ subunit. Other anti-convulsant drugs like phenytoin, diazepam, carbamazepine, valproate, and phenobarbitone do not compete for gabapentin binding. Ligands for other calcium channel subtypes including verapamil, the omega-conotoxins MVIIC and GVIA, ryanodine, caffeine, capsaisin and MK801 do not interact with the gabapentin binding site. Electrophysiological data indicate that gabapentin effectively blocks Ca2+ currents in a cortical neuron preparation and selectively reduces whole-cell Ca2+ currents in a voltage-dependent fashion in cultured DRG neurons.
Compounds of the present invention are α2δ voltage-gated calcium channel ligands and have utility in treating or preventing disorders associated with α2δ voltage-gated calcium channels.